Preventive effect of intravesical ozone supplementation on n-methyl-n-nitrosourea-induced non-muscle invasive bladder cancer in male rats.

Although non-muscle invasive bladder cancer (NMIBC) is widely seen in men, most laboratory studies of new intravesical therapies to prevent NMIBC have been conducted on female animals. In addition, ozone (O3) has been shown to be a beneficial agent as an intravesical application in the treatment of various disorders. In the current study, we evaluated the immunohistopathological and oxidative-antioxidative effects of intravesical O3 treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O3 only (n=15), MNU only (n=15), and MNU+O3 (n=15). The MNU-only and MNU+O3 groups received MNU, and the O3-only group received saline every other week for 10 weeks. The MNU-only group received 1 ml saline in place of O3 treatment, whereas the O3-only and MNU+O3 groups were treated with 1 ml 25 µg/ml O3 between the 7th and 12th weeks. Rat bladders were collected in the 15th week for immunohistopathology and oxidant-antioxidant quantitation. Oxidant-antioxidant parameters were determined by ELISA. Although all surviving rats in the MNU-only group had preneoplastic (4/11, 36.4%) or neoplastic changes (7/11, 63.6%), a completely normal urothelium was observed in 2 rats (2/12, 16.7%) in the MNU+O3-group (P=0.478). More high-grade lesions were observed in the MNU-only group (4/11, 36.4%) than in the MNU+O3 group (1/12, 8.3%) (P=0.120). All oxidant-antioxidant parameters significantly increased (P<0.05) in the O3-only group compared with the sham group. However, only antioxidant superoxide dismutase was remarkably higher (178.9%, P=0.060) in the MNU+O3 group compared with the MNU-only group. This is the first methodologically and pathologically well-described male rat orthotopic bladder carcinogenesis model with intravesical MNU and administration of O3 in NMIBC.

Effects of erdosteine on bleomycin-induced lung fibrosis in rats.

This study was designed to examine the effects of erdosteine on bleomycin (BLM)-induced lung fibrosis in rats. Thirty-three Sprague-Dawley rats were divided randomly into three groups, bleomycin alone (BLM), bleomycin + erdosteine (BLM + ERD), and saline alone (control). The BLM and BLM + ERD groups, were given 2.5 mg/kg BLM intratracheally. The first dose of oral erdosteine (10 mg/kg/day) in the BLM + ERD group was started 2 days before BLM administration and continued until animals were sacrificed. Animals were sacrificed 14 days after intratracheal instillation of BLM. The effect of erdosteine on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and biochemical measurements of lung tissue superoxide dismutase (SOD) and glutathione (GSH) as antioxidants, malondialdehyde (MDA) as an index for lipid peroxidation, and nitrite/nitrate levels. Bleomycin-induced lung fibrosis as determined by lung histology was prevented with erdosteine (grades of fibrosis were 4.9, 2.3, and 0.2 in BLM, BLM + ERD, and control groups, respectively). Erdosteine also prevented bleomycin-induced increase in MDA (MDA levels were 0.50 +/- 0.15, 0.11 +/- 0.02, and 0.087+/- 0.03 nmol/mg protein in BLM, BLM + ERD, and control groups, respectively) and nitrite/nitrate (nitrite/nitrate levels were 0.92 +/- 0.06, 0.60 +/- 0.09, and 0.56+/- 0.1 micromol/mg protein in BLM, BLM + ERD, and control groups respectively) levels. Bleomycin-induced decrease in GSH and SOD levels in the lung tissue also prevented by erdosteine [(GSH levels were 213.5 +/- 12.4, 253.2+/- 25.2, and 287.9+/- 34.4 nmol/mg protein) (SOD levels were 1.42+/- 0.12, 1.75+/- 0.17, and 1.89+/- 0.09 U/mg protein) in BLM, BLM + ERD, and control groups respectively]. Erdosteine prevented bleomycin-induced increases in total cell number and neutrophil content of the BAL fluid. In conclusion, oral erdosteine is effective in prevention of BLM-induced lung fibrosis in rats possibly via the repression of neutrophil accumulation, inhibition of lipid peroxidation, and maintenance of antioxidant and free radical scavenger properties.

Effects of vitamins E, A and D on MDA, GSH, NO levels and SOD activities in 5/6 nephrectomized rats.

BACKGROUND: Excessive generation of reactive oxygen species (ROS) contributes to the process of progressive renal injury in a variety of clinical and experimental renal diseases. The present study was designed to test the hypothesis that treatment with vitamins decreases renal injury in chronic renal failure (CRF). METHODS: Forty male Sprague-Dawley rats were divided into 5 groups: group 1, control; group 2, 5/6 nephrectomy (CRF); other groups 5/6 nephrectomy and injected vitamins (E, A, D). After 8 weeks, urea, creatinine and renal tissue malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and superoxide dismutase (SOD) activities were determined. RESULTS: Renal tissue MDA levels were significantly lower in the control and Vit E groups compared to that of the CRF, Vit A and Vit D groups. GSH levels were significantly higher in the control group compared to that of other groups. However, GSH levels were significantly lower in the control group than those in the other groups. SOD activities of the control group were significantly higher than those in the other groups. SOD activities were significantly decreased in the Vit E group compared to the Vit A and Vit D groups. Tissue NO levels of control group were significantly increased compared to the other groups. CONCLUSION: According to this study, Vit E may at least in part prevent tissue injury by acting as a free radical scavenger.

Homocysteine and nitric oxide levels in plasma of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma.

PURPOSE: To evaluate plasma total homocysteine (tHcy) and nitric oxide (NO) marker levels in patients with pseudoexfoliation syndrome (PXS), pseudoexfoliation glaucoma (PXG), primary open-angle glaucoma (POAG), and normal controls. METHODS: This cross-sectional, prospective study involved 19 patients with POAG, 18 with PXS, 22 with PXG, and 20 control subjects. Fasting tHcy levels of all study participants were determined using a fluorescence polarization immunoassay method. Quantitation of total nitrate was based on the Griess reaction, in which a chromophore with a strong absorbance at 545 nm is formed by reaction of nitrite with a mixture of naphthylethylenediamine and sulphanilamide. RESULTS: The mean plasma homocysteine level was statistically significantly elevated in the PXS (p=0.033) and the PXG (p=0.023) groups but not in the POAG group (p=0.996) when compared with the control group. Multiple logistic regression analyses comparing the various patient groups with the single control group indicated that elevation in plasma homocysteine concentration was a significant risk factor for PXS (odds ratio per 1 micromol/l increase in homocysteine concentration=2.05, 95% CI=1.19-3.52) and PXG (odds ratio per 1 micromol/l increase in homocysteine concentration=1.36, 95% CI=1.00-1.85) but was not a significant risk factor for POAG (odds ratio per 1 micromol/l increase in homocysteine concentration=0.99, 95% CI=0.78-1.26). NO markers levels were found to be slightly higher in PXS and PXG patients than control and POAG patients but the differences were not statistically significant (p=0.151). Multiple logistic regression analyses comparing the various patient groups with the single control group indicated that elevation in NO marker concentration was not a significant risk factor for PXS (odds ratio per 1 micromol/l increase in NO concentration=1.00, 95% CI=0.99-1.01), PXG (odds ratio per 1 micromol/l increase in NO concentration=1.00, 95% CI=0.99-1.00) and POAG (odds ratio per 1 micromol/l increase in NO concentration=0.99, 95% CI=0.99-1.00). No statistically significant correlations were observed between plasma tHcy and NO markers in study groups (p>0.05). CONCLUSION: Elevated levels of homocysteine in pseudoexfoliation patients with and without glaucoma may partly explain the increased risk of vascular disease among patients with pseudoexfoliation. No significant difference was found in plasma NO markers among the POAG, PXS, PXG, and the control subjects.